Plasma Free T4 Research Articles

Effects of Clofibrate on Salt Loading‐Induced Hypertension in Rats

The effects of clofibrate on the hemodynamic and renal manifestations of increased saline intake were analyzed. Four groups of male Wistar rats were treated for five weeks: control, clofibrate (240 mg/kg/day), salt (2% via drinking water), and salt + clofibrate. Body weight, systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, HR, and morphologic, metabolic, plasma, and renal variables were measured. Salt increased SBP, HR, urinary isoprostanes, NOx, ET, vasopressin and proteinuria and reduced plasma free T4 (FT4) and tissue FT4 and FT3 versus control rats. Clofibrate prevented the increase in SBP produced by salt administration, reduced the sodium balance, and further reduced plasma and tissue thyroid hormone levels. However, clofibrate did not modify the relative cardiac mass, NOx, urinary ET, and vasopressin of saline-loaded rats. In conclusion, chronic clofibrate administration prevented the blood pressure elevation of salt-loaded rats by decreasing sodium balance and reducing thyroid hormone levels.

Dioxin‐like and perfluorinated compounds in pigs in an Indian open waste dumping site: Toxicokinetics and effects on hepatic cytochrome P450 and blood plasma hormones

Dioxins and related compounds (DRCs) and perfluorinated compounds were measured in the livers of pigs (Sus scrofa) collected from an open waste dumping site in South India. Hepatic concentrations of DRCs and perfluorooctanesulfonate (PFOS; up to 200 ng/g wet wt) were significantly higher in male and female pigs, respectively, collected from the dumping site than in those from a reference site. Results suggest that dumping sites are a source of DRCs and PFOS. Hepatic concentrations of DRCs in piglets were higher than in mothers, especially for the congeners with molecular weights in the range of 360 to 400, implying congener-specific maternal transfer of DRCs in swine. Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans and some non-ortho dioxin-like polychlorinated biphenyls (PCBs) in the liver of pigs were higher than those in the adipose fat and muscle of the same specimens. In addition, the liver-to-adipose concentration ratios for each congener had a significant positive correlation with the levels of hepatic cytochrome P450 (CYP)1A-like protein, suggesting congener-specific and CYP1A-dependent hepatic sequestration of DRCs in the swine. Total hepatic 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs; 8.9-350 pg/g fat wt) had a significant positive correlation with CYP1A-like protein expression (r=0.56, p=0.012), suggesting the induction of CYP1A by DRCs. However, the total TEQs had a significant negative correlation with CYP4A-like protein (r=-0.49, p=0.029), suggesting repression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-mediated signaling pathway by DRCs. Decreases in plasma total thyroxine (T4), free T4, and immunoglobulin (Ig) G were also found in pigs from the dumping site compared with those from the reference site. This study provides insight into the toxicological impacts of DRCs and perfluorinated compounds in wild animals from open waste dumping sites.

Hypercholesterolaemia in anorexia nervosa: Frequency and changes during refeeding

High total cholesterol (TC) is common in patients with anorexia nervosa (AN), but its mechanisms remain unclear. Patients and methods We prospectively studied plasma lipoprotein (LP), haptoglobin, free (f) T3, fT4, TSH, transthyretin and albumin in 120 malnourished adult AN patients (BMI: 13.5 ± 1.5 kg/m 2), 116 non-AN malnourished patients and 119 healthy subjects, matched for age and gender. Results In 18% of our AN patients, TC was higher than 270 mg/100 mL (in non-AN: 5%; P < 0.01). TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and HDL2 levels were higher in AN patients than in non-AN patients ( P < 0.001). Low TC (<150 mg/100 mL) and LP levels were observed in 8% of AN patients, but only when BMI was less than 13 kg/m 2. Cholesterol ester transfer protein (CETP) activity was higher in AN patients than in healthy subjects. LP was positively correlated with BMI, albumin, fT3 and haptoglobin levels. In AN patients, there was a biphasic LP profile (low values when BMI was very low, normal values in an intermediate state, and high values when BMI was highest and where bulimia was also present). Conclusion In AN, both high and low cholesterol-rich LP levels were observed. Low T3 and low catabolism allow LP to be maintained, while CETP activity increases cholesterol turnover as an adaptation to its low intake. In severely malnourished AN patients, this fails and LP drops. On the other hand, LP values were higher in the bingeing–purging type of AN than in the restrictive type. Recovery from AN results in the normalization of the LP profile.

Macrophage Migration Inhibitory Factor in Pediatric Patients Undergoing Surgery for Congenital Heart Repair

Macrophage migration inhibitory factor (MIF), a proinflammatory mediator, has been shown to be elevated following heart surgery in adults and may be associated with several postoperative complications, including cardiac and pulmonary dysfunction. In this study, we aimed to measure perioperative plasma MIF, interleukin (IL)-8, and free T4 in 20 children age <4 years undergoing surgical repair of congenital heart lesions with left ventricular volume overload, and to determine whether the response of these mediators determined postoperative outcomes. Plasma samples were obtained preoperatively, immediately on arrival in the pediatric intensive care unit (PICU), and at 12, 24, and 48 h. Patients were continuously monitored in the PICU, and data were recorded daily for therapeutic and monitoring procedures that reflected the invasiveness, intensity, and complexity of care rendered (therapeutic interventional scoring system, TISS). Preoperative plasma MIF, IL-8, and free T4 were not different from age-matched healthy children. However, plasma MIF and IL-8 increased significantly 2 h after completion of cardiopulmonary bypass, and then normalized within 24 h. Peak postoperative levels of MIF (48 +/- 24 ng/mL) and IL-8 (79 +/- 57 pg/mL) correlated significantly with duration of cardiopulmonary bypass. The magnitude of the postoperative increase in plasma MIF was associated with increased number of days required for mechanical ventilation (r = 0.553; P = 0.012), and peak plasma IL-8 correlated significantly with the fraction of inhaled oxygen (FiO(2)) required immediately after surgery (r = 0.510; P = 0.02). Higher circulating MIF levels correlated significantly with increased inotropic support requirements on the second postoperative day, whereas higher postoperative IL-8 levels were associated with higher TISS scores, suggesting increased need for postoperative medical care. These data suggest a potential negative effect of high circulating levels of MIF in the immediate postoperative period on respiratory and cardiovascular functions, and support the development of therapeutic strategies targeting MIF function in this clinical setting.

The involvement of thyroid hormones and cortisol in the osmotic acclimation of Solea senegalensis

The peripheral conversion of the prohormone 3,5,3′,5′-tetraiodothyronine (T4) to the biologically active 3,5,3′-triiodothyronine (T3), via enzymatic deiodination by deiodinases, is an important pathway in thyroid hormone metabolism. The aim of this study was to test if thyroid hormones and cortisol, as well as the outer ring deiodination (ORD) metabolic pathway, are involved in the osmoregulatory response of Senegalese sole ( Solea senegalensis, Kaup 1858). We measured osmoregulatory and endocrine parameters in immature juveniles S. senegalensis acclimated to seawater (SW, 38‰) and that were transferred and allowed to acclimate to different salinities (5‰, 15‰, 38‰ and 55‰) for 17 days. An adjustment and a chronic regulatory period were identified following acclimation. The adjustment period immediately follows the transfer, and is characterized by altered plasma osmolalities. During this period, plasma cortisol levels increased while plasma free T4 (fT4) levels decreased. Both hormones levels returned to normal values on day 3 post-transfer. In the adjustment period, renal and hepatic ORD activities had increased concomitantly with the decrease in plasma fT4 levels in fishes transferred to extreme salinities (5‰ and 55‰). In the chronic regulatory period, where plasma osmolality returned to normal values, plasma cortisol had increased, whereas plasma fT4 levels decreased in animals that were transferred to salinities other than SW. No major changes were observed in branchial ORD activity throughout the experiment. The inverse relationship between plasma cortisol and fT4 suggests an interaction between these hormones during both osmoregulatory periods while ORD pathway can be important in the short-term adjustment period.

The adaptation and relationship of FGF‐23 to changes in mineral metabolism in Graves’ disease

The aim of this study was to observe the changes in bone and mineral metabolism and to confirm the regulation of fibroblast growth factor-23 (FGF-23) in untreated Graves' disease. The study comprised 39 patients, with or without Graves' disease. The Graves' disease group was made up of 21 newly diagnosed patients, enrolled before starting treatment. Their disease was determined by biochemical and radiological means. The control group was composed of 18 people who were proven to be euthyroid without any diseases affecting bone and mineral metabolism. FGF-23, calcium, phosphate, PTH, 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels and bone turnover markers were compared between these groups. Serum calcium and phosphate, plasma FGF-23 and free T4 were significantly higher in the Graves' disease group than in the healthy control group (P < 0.05). The bone turnover markers serum osteocalcin and C-terminal cross-linked telopeptide of type 1 collagen (s-CTx) were also significantly elevated in the Graves' disease group, and had a positive correlation with free T4 levels. However, there was no significant decrease in PTH and 1,25(OH)2D in the Graves' disease group. Plasma levels of FGF-23 exhibited a positive correlation with serum phosphate levels and with free T4 levels (P < 0.05). These findings suggest that FGF-23 is physiologically related to serum phosphate homeostasis, as indicated indirectly by the changes in bone and mineral metabolism, in untreated Graves' disease.

Thyroid and hypoxic stress in the newtTriturus carnifex

When specimens of the newt Triturus carnifex, under anaesthesia by submersion in a 0.2% chlorbutol solution for 25 min, are isolated in a respiratory chamber at 18 degrees C containing water with only 1.3 ppm of oxygen, they consume the oxygen completely in about 3 hr, but they can stay alive for many more hours and wake up with no apparent exterior consequences. Hypoxia induces rapid onset of hepatic steatosis and melanosis, as well as a controlled haemolytic process involving a pool of red blood cells of the same order of size as that held as a reserve in the spleen by animals in an aerial habitat. At the origin of the phenomena is an intense response by the hypophysis, histologically detectable 1 hr from the onset of treatment and confirmed 2 hr later by a highly significant increase in the plasma thyroidstimulating hormone (TSH) concentration compared with the controls (41.5 +/- 13.7 microU/L vs. 15.5 +/- 6.2; P < 0.005). The thyroid follicles react by reabsorbing their colloid, but instead of an increase in the plasma free T3 and T4 concentrations, fT3 falls significantly (1.5 +/- 0.3 pg/mL vs., the 2.4 +/- 0.7; P < 0.05), whereas fT4 remains stationary (4.0 +/- 0.5 pg/mL vs. 4.6 +/- 0.8; N.S.). After 6 hr, the plasmatic TSH concentration is still higher than in the controls (27.0 +/- 3.0 microU/L vs. 15.5 +/- 6.2; P < 0.05), whereas fT3 and fT4 remain stable (1.5 +/- 0.3 and 4.4 +/- 0.5 pg/mL, respectively). If T3 or T4 labelled with 125I is administered prior to hypoxia, after 6 hr of treatment the radioactivity is found to be limited exclusively to the liver and kidney; the thyroid, gall bladder and gut result negative, and this does not agree with hypotheses of hormone inactivation by deiodination, sulphation or glucuronidation. This apparently peculiar endocrine path has not been observed in previous studies on hypoxia in vertebrates, because the experiments were always designed to analyse plasma hormone levels after at least 24 hr of hypoxia or during chronic treatments, losing the most interesting phases of the endocrine response. The possibility that the hypoxic newt possesses alternative or complementary metabolic pathways to anaerobic glycolysis to sustain steatogenesis and melanogenesis and maintain the same cardiac activity as the controls is briefly discussed.

Testis Structure and Function in a Nongenetic Hyperadipose Rat Model at Prepubertal and Adult Ages

There are few data for hormonal levels and testis structure and function during postnatal development in rats neonatally treated with monosodium L-glutamate (MSG). In our study, newborn male pups were ip injected with MSG (4 mg/g body weight) every 2 d up to 10 d of age and investigated at prepubertal and adult ages. Plasma levels of leptin, LH, FSH, prolactin, testosterone (T), corticosterone, and free T4 (FT4) were measured. MSG rats displayed elevated circulating levels of corticosterone and hyperadiposity/hyperleptinemia, regardless of the age examined; conversely, circulating prolactin levels were not affected. Moreover, prepubertal MSG rats revealed a significant (P < 0.05) reduction in testis weight and the number of Sertoli (SC) and Leydig cells per testis. Leptin plasma levels were severalfold higher (2.41 vs. 8.07; P < 0.05) in prepubertal MSG rats, and these animals displayed plasma LH, FSH, T, and FT4 levels significantly decreased (P < 0.05). Taken together, these data indicate that testis development, as well as SC and Leydig cell proliferation, were disturbed in prepubertal MSG rats. Adult MSG rats also displayed significantly higher leptin plasma levels (7.26 vs. 27.04; P < 0.05) and lower (P < 0.05) LH and FSH plasma levels. However, T and FT4 plasma levels were normal, and no apparent alterations were observed in testis structure of MSG rats. Only the number of SCs per testis was significantly (P < 0.05) reduced in the adult MSG rats. In conclusion, although early installed hyperadipose/hyperleptinemia phenotype was probably responsible for the reproductive axis damages in MSG animals, it remains to be investigated whether this condition is the main factor for hypothalamus-pituitary-gonadal axis dysfunction in MSG rats.

Impact of chlorpyrifos on cerebrum and cerebellum maturity in suckling rats

The purpose of our study is to assess the effect of chlorpyrifos (CPF) on rat cerebral and cerebellar maturity during the suckling period. Female Wistar rats were given 0.2 g L−1 of CPF in drinking water, equivalent to 40 mg kg−1 of body weight day−1, from day zero until day ten after delivery. In treated pups, plasma butyrylcholinesterase (BuChE) activity was inhibited by 70%. Cerebrum and cerebellum acetyl-cholinesterase (AchE) activities were reduced by 71 and 75%, respectively. The results suggest that CPF was distributed in pup tissues through the milk of lactating mothers, resulting in inhibition of AchE activities. At age 10 days, the CPF-treated pups showed a 28% decrease in body weight, a 23 and 41% decrease in plasma free T3 and T4 levels and reduction in cerebral and cerebellar protein content by 36 and 38%, respectively. Consistent histological changes were found in the cerebellum of CPF treated pups, with the external granular layer being markedly developed, the Purkinje cell bodies being poorly differentiated and abnormally distributed into the internal granular layer.

Thyroid hormone status in gray seal (Halichoerus grypus) pups from the baltic sea and the atlantic ocean in relation to organochlorine pollutants

Marine apex predators, such as the gray seal (Halichoerus grypus), are exposed to high concentrations of organochlorine (OC) compounds via biomagnification in the food web. These lipophilic pollutants are transferred from the female to her offspring during lactation, and there is particular concern for endocrine disruption in the offspring. Herein we examined associations between the blubber concentrations of polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and metabolites, chlordanes, hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB), and plasma concentrations of thyroid hormones (thyroxine [T4] and tri-iodothyronine [T3]) in free-ranging, newly weaned gray seal pups from the Baltic Sea and the Norwegian waters of the Atlantic Ocean. Concentrations of total T3 (TT3) and free T3 (FT3) were significantly lower in the polluted seals from the Baltic Sea. Blubber concentrations of the sum of the analyzed PCB congeners (sigmaPCBs) and the sum of the DDT compounds (sigmaDDTs) were correlated negatively with plasma TT3 and FT3 concentrations. The results from this study indicate that OCs may affect levels of thyroid hormones in free-ranging gray seal pups, and that more focus should be put on T3 when addressing the possible effects of OCs on thyroid hormone function and status in nonrodent species.

Thyrotropin-secreting pituitary adenoma:a clinicopathological analysis of seven cases

To study the clinicopathological features of thyrotropin-secreting pituitary adenoma (TSH adenoma). Clinical and pathological features of 7 TSH adenoma cases were studied by review of patients' medical records, light and electronic microscopy, and immunohistochemistry. All seven patients presented with clinical hyperthyroidism and high levels of plasma free T3, free T4, total T3 and total T4. The levels of TSH failed to be suppressed by thyroxin administration. MRI showed macro or giant pituitary adenomas in all seven patients with tumor diameters ranging from 2.0 to 5.0 cm. Under light microscope, there were 5 cases of chromophobe cell adenoma, 1 case of acidophil cell adenoma, and 1 case of mixed acidophil and chromophobe cell adenoma. Immunohistochemical stains showed a strong positivity of TSH in all the tumors, PRL positive cells in 1 tumor, GH positive cells in 2 tumors and scattered GH and PRL double positive cells in 3 tumors. Ki-67 proliferation index ranged from 0 approximately 0.4%. P53 immunostain was negative in all tumors. After initial surgery, 2 cases had recurrences. However, the Ki-67 proliferation index was not elevated in these two tumors. The histological features of TSH pituitary adenomas are heterogeneous with chromophobe as the most common subtype. Secretion of TSH was detected by immunohistochemistry in all cases. P53 mutation is not a feature of TSH adenoma and the proliferation marker, such as Ki-67, may not predict clinical behavior of the tumor. Recurrence is likely due to incomplete resection.

25 Recovery from Mitral Insufficiency after Removal of an Autonomous Hyperfunctioning Thyroid Nodule Causing Hyperthyroidism in a 4-Year-Old Girl

Mitral valve insufficiency from hyperthyroidism is believed to stem from longstanding insidious disease and is considered to be irreversible. To describe a child who presented with hyperthyroidism and mitral valve insufficiency which significantly decreased after correction of hyperthyroidism. In this 4.4-year-old girl with no significant family or personal history, tachycardia (150 bpm), hypertension (150/80 mmHg), a heart murmur and an asymmetric goiter were noted fortuitously during a routine pediatric visit prompted by the premature loss of a deciduous tooth. Height had increased from +2.1 SD at 2 y to +3.1 SD while there had been relative loss of weight (from +2.9 SD to +1.5 SD). She had been hyperactive for six months, but had no other sign or symptom of hyperthyroidism. Bone age was 7 years. Plasma free T4 was 57.8 pmol/L (N 11.5–22.7) and total T3 was 8.7 nmol/L (N 1.2–3.0). Plasma TSH was undetectable, as were antibodies to thyroperoxidase and to the TSH receptor (TSHR). A thyroid scan with 99mTc revealed intense uptake on the right side and no uptake on the left. Cervical ultrasound revealed the presence of a three cm nodule in the right thyroid lobe; the left thyroid lobe was small but visible. Cardiac evaluation revealed moderate mitral valve insufficiency with left atrial dilatation and the patient was put on beta-blockers in preparation for surgery. Right hemithyroidectomy was performed two weeks later. A well-encapsulated nodule measuring 3×2.5×1.6 cm occupied most of the right lobe. The pathological diagnosis was follicular adenoma. DNA was extracted from the thyroid nodule and from the patient's leucocytes. Direct sequencing revealed a previously described (D663H) constitutively activating mutation in the TSHR in the thyroid nodule but not in leucocytes (somatic mutation). One month after surgery, the patient became hypothyroid (TSH 30 mU/L (N 0.3–5), free T4 7.5 pmol/L) and was started on levothyroxine replacement. She had dramatic improvement in her cardiac function with only mild residual mitral valve insufficiency three months after surgery. This rare case illustrates the recovery from mitral valve insufficiency in a young child with hyperthyroidism from an autonomous hyperfunctioning thyroid nodule. We speculate that this favourable outcome may be due to the patient's young age and/or to the relatively short duration of her hyperthyroidism.

Effects of triiodothyronine on 5-HT 1A and 5-HT 1B autoreceptor activity, and postsynaptic 5-HT 1A receptor activity, in rat hypothalamus: lack of interaction with imipramine

Triiodothyronine (T3) is effective in both augmenting and accelerating the therapeutic response to antidepressant drugs, especially tricyclics, and there is evidence from both human and animal studies that it acts on serotonergic neurotransmission. In this work we examined the effects of T3 alone and together with imipramine on 5-HT levels in the hypothalamus and on 5-HT 1A and 5-HT 1B autoreceptor sensitivity, using in vivo microdialysis in the rat. The effects of T3 on postsynaptic 5-HT 1A receptor activity in the hypothalamus were also determined using a neuroendocrine challenge procedure. T3 administered daily at 20 μg/kg s.c. for 2 weeks reduced the sensitivity of 5-HT 1A autoreceptors which control 5-HT release, as measured by the effect of 8-OH-DPAT to decrease 5-HT in the hypothalamus, and also the sensitivity of hypothalamic 5-HT 1B receptors as measured by the effect of the 5-HT 1B receptor agonist CP 93129 to decrease 5-HT release. Imipramine at 10 mg/kg daily for 4 weeks by osmotic minipump reduced 5-HT 1A autoreceptor activity, as measured by the effect of 8-OH-DPAT in the hypothalamus, but the combination of T3 and imipramine given for 2 weeks did not affect either 5-HT 1A or 5-HT 1B autoreceptor activity. T3 at 20 μg/kg s.c. given daily for 1 week also reduced the sensitivity of postsynaptic 5-HT 1A receptors in the hypothalamus, as measured by injection of 8-OH-DPAT and determination of the plasma ACTH and corticosterone responses. Animals which received T3 for 7 days showed a dose-dependent reduction in plasma free T4 levels but no change in total T3 levels. We conclude that while T3 alone affects both presynaptic and postsynaptic components of the serotonergic system, these effects may not be responsible for the therapeutic acceleration action seen with a combination of a tricyclic drug and T3.

Efeitos da asfixia perinatal sobre os hormônios tireoidianos

OBJETIVO: verificar o efeito da asfixia perinatal sobre os hormonios tireoideos. METODOS: Foi realizado um estudo de caso-controle, no hospital de Clinicas de Porto Alegre, envolvendo 17 recem-nascidos a termo asfixiados (A) e 17 nao-asfixiados (N), pareados conforme a cor, sexo, tipo de parto, idade gestacional e peso de nascimento. Foram coletados T4, T3, T4 livre, T3 reverso e TSH do sangue do cordao e do recem-nascido com 18 a 24 horas de vida, entre os que sofreram ou nao asfixia perinatal. RESULTADOS: No sangue de cordao, nao houve diferenca na dosagem dos hormonios tireoideos, com excecao do T3 reverso, que foi mais elevado no grupo que sofreu asfixia [mediana (percentis 25-75) :A= 2(1,4-2); N= 1,41(1,13-1,92); p=0,037]. Com 18 a 24 horas de vida, foram significativamente menores no grupo de asfixiados, com excecao do T3 reverso, que foi semelhante entre os dois grupos [media ± DP: T4 A= 9,79 ± 2,59; N=14,68 ± 3,05; p < 0,001/ mediana T3 A = 40,83(37,4-80,4) ; N= 164(56,96-222,5); P=0,003/ media ± DP T4 livre A =1,85 ± 0,92; N = 2,8 ± 0,74; p = 0,004/ mediana T3 reverso A= 1,54(1,16-1,91); N = 1,31(0,87-2); p=0,507/ TSH A= 9,1(6,34-12,95); N=14,5(12,9-17,85); p=0,008]. CONCLUSOES: Nossos dados sugerem que os niveis diminuidos de T4, T4 livre e T3 no recem-nascido asfixiado com 18 a 24 horas de vida sao secundarios aos niveis diminuidos de TSH. Alem disso, os valores baixos de T3 e normais de T3 reverso podem refletir alteracao no metabolismo periferico do T4.

Chronic daily ethanol and withdrawal: 5. Diurnal effects on plasma thyroid hormone levels.

We previously demonstrated that chronic daily ethanol consumption and daily withdrawal by male rats in a modified ethanol liquid diet paradigm produced (a) chronically increased adrenal glucocorticoid activity; (b) decreased plasma testosterone; (c) decreased forebrain proopiomelanocortin gene expression; and (d) corresponding alterations in plasma leptin levels-all of which are consistent with reported changes during alcohol abuse and alcoholism. Each of these systems interact with hypothalamo-pituitary-thyroid (HPT) regulation, and links between chronic alcohol abuse and thyroid dysfunction have been suggested by both human and rat studies. Accordingly, we have begun to investigate potential HPT mediation of, or response to, alterations in these systems by investigating plasma thyroid hormone levels in the same chronic daily ethanol/ withdrawal paradigm. Chronic daily episodes of ethanol consumption and withdrawal by male Sprague- Dawley rats decreased plasma levels of free (non-protein- bound) triiodothyronine (T3) (p < 0.01) and free thyroxine (T4) (p < 0.05) in the morning but not in the afternoon, relative to both ad libitum-fed and pair-fed controls (n = 9/treatment). Plasma total T4 levels were likewise suppressed (p < 0.01) in the morning, whereas total T3 levels were increased (p < 0.05) in the afternoon. These changes eliminated normal diurnal patterns (higher in the morning) of plasma free T3, free T4, and total T3 concentrations. Three weeks after cessation of ethanol consumption, morning plasma levels of free and total T3 and T4, as well as plasma thyroid-stimulating hormone (TSH), were all not significantly changed by the prior ethanol consumption or pair-feeding. These results reveal that plasma thyroid hormone concentrations are suppressed in a time of day dependent manner by chronic daily ethanol consumption and daily withdrawal in this model of chronic ethanol abuse. During subsequent long-term "abstinence," these thyroid hormones returned to control levels. These results are consistent with evidence that thyroid function is commonly diminished in alcoholism, with variable reports of recovery during abstinence. Further investigations with this rat model of daily ethanol consumption and daily withdrawal will help resolve interactions and roles of the HPT axis in alcohol abuse.

Pinealectomy and Zinc Deficiency Have Opposite Effects on Thyroid Hormones in Rats

The present study was conducted to investigate how pinealectomy and zinc deficiency separately or in combination affected thyroid hormones in rats. The study was carried out on 40 Sprague–Dawley male rats. The rats were equally allocated to four groups: Group 1 (control group), Group 2 (zinc‐deficient group), Group 3 (pinealectomized group) and Group 4 (pinealectomized and zinc‐deficient group). At the end of a 4‐week study period, the rats were decapitated and blood samples were taken. The samples were examined in terms of plasma zinc, melatonin, free and total T3, T4, and TSH. It was found that free T3 and T4 levels in the pinealectomized group (Group 3) were higher than all others ( p < 0.01) while free T3, T4, and TSH levels in the zinc‐deficient group (Group 2) were lower than all others ( p < 0.01). Free T3 and T4 levels in the pinealectomized zinc‐deficient group (Group 4) were lower than those in Groups 1 and 3 and higher than those in Group 2 ( p < 0.01). The findings obtained at the end of the study period show that pinealectomy has a stimulating and zinc deficiency has a suppressing effect on thyroid hormones and that the suppressing effect caused by zinc deficiency is partially balanced by pinealectomy.

Euthyroid sick syndrome in acute ischemic syndromes.

The purposes of this study were to assess the occurrence of euthyroid sick syndrome in patients with acute myocardial infarction (AMI) or unstable angina (UA), and the relationship with beta-blocker or thrombolytic therapy. Plasma triiodothyronine (T3), reverse T3 (rT3), free T3 (FT3), thyroxine (T4), free T4 (FT4), thyroid-stimulating hormone (TSH), thyroxine-binding globulin (TBG), and albumin (ALB) levels were determined in 95 patients (59 males, 36 females, aged 58.4+/-9) with AMI and 19 patients (13 males, 6 females aged 54.7+/-12.3) with UA for 5 consecutive days from the onset of the acute syndrome and 1 month later. Patients were divided according to beta-blocker therapy and thrombolytic therapy. There was a significant T3 decrease and rT3 increase in all patients during the first 5 days following admission (p < 0.05). FT3 and FT4 remained unchanged during the study. In patients with complicated infarctions, the rT3 increase and the T3 decrease were significantly greater compared to those with uncomplicated infarctions (p<0.03). TSH, T4, TBG, and ALB were significantly (p<0.05) decreased only in complicated infarctions. No differences were observed between patients with or without thrombolysis or patients with or without beta-blocker treatment. The apparent decrease in T3, the increase in rT3 levels and the decreased TSH and T4 levels, show clearly that the euthyroid sick syndrome (low T3) occurs not only in AMI but also in UA. In addition, these hormonal changes are not affected by beta-blocker therapy and thrombolysis does not influence the occurrence of the syndrome. The degree of T3 decrease is proportional to the severity of cardiac damage and may have a possible prognostic value.

Dynamics of the plasma concentrations of TSH, FT4 and T3 following thyroxine supplementation in congenital hypothyroidism.

The dynamics of the plasma concentrations of various diagnostic determinants of thyroid function were analysed in children with congenital hypothyroidism (CH) after the start of T4 supplementation. The description of the biochemical dynamics of TSH and free T4 (FT4) during the first period of thyroxine treatment is important to depict the practical outlines of the initial dosage of T4 and dosage adjustments for newborns with variable forms of CH. A retrospective analysis was performed of frequent plasma TSH, total T4 (T4), FT4 and total T3 (T3) measurements in 30 CH neonates during the first weeks of treatment, treated with initial daily T4 dosages ranging from 4.8 to 11.1 microg/kg. A 50% reduction in the initial plasma TSH concentration was achieved after 3-4 days of treatment, independent of CH severity. At a median of 32 days after the start of T4 supplementation, plasma TSH ranged between 0.4 and 4.0 mU/l. The mean interval needed for FT4 to reach the age-related normal values (12-29 pmol/l) was 3 days. The increase in plasma T3 concentrations levelled off within a few days, when T4 reached concentrations of around 100 nmol/l. Plasma T3 and FT4 concentrations reach the normal range a few days after thyroxine treatment is started. By contrast, normalization of plasma TSH concentration takes several weeks. At the time that plasma TSH is normalized, CH neonates show a higher range of plasma FT4 concentrations than the normal range. When TSH normalization is the goal of treatment in CH, the target range for plasma FT4 during treatment in the first months needs to be adapted. During the first month of treatment the plasma TSH concentration is not helpful in assessing the proper T4 supplementation dosage. Once plasma TSH has reached normal values, it becomes a reliable determinant in addition to plasma FT4.

Hypothalamic thyrotropin-releasing hormone mRNA responses to hypothyroxinemia induced by sleep deprivation.

Sleep deprivation in rats results in progressive declines in circulating concentrations of both total and free thyroxine (T(4)) and triiodothyronine (T(3)) without an expected increase in plasma thyroid-stimulating hormone (TSH). Administration of thyrotropin-releasing hormone (TRH) results in appropriate increases in plasma TSH, free T(4), and free T(3) across experimental days, suggesting deficient endogenous TRH production and/or release. This study examined transcriptional responses related to TRH regulation following sleep deprivation. In situ hybridization was used to detect and quantitate expression of mRNAs encoding prepro-TRH and 5'-deiodinase type II (5'-DII) in brain sections of six rats sleep deprived for 16-21 days, when there was marked hypothyroxinemia, and in sections from animals yoked to the experimental protocol as well as from sham controls. TRH transcript levels in the paraventricular nucleus (PVN) were essentially unchanged at 15-16 days but increased to about threefold control levels in three of four rats sleep deprived for 20-21 days, a change comparable to that typically found in prolonged experimental hypothyroidism. There was no evidence for suppression of 5'-DII mRNA levels, which would be a sign of T(3) feedback downregulation of neurons in the PVN. A failure to increase serum TSH in response to hypothyroxinemia and to increased prepro-TRH mRNA expression indicates that alterations in posttranscriptional stages of TRH synthesis, processing, or release likely mediate the central hypothyroidism induced by sleep deprivation.

Fetal and Maternal Thyroid Hormone Responses to Ethanol Exposure During the Third Trimester Equivalent of Gestation in Sheep

Background: Abnormal thyroid hormone system function in the mother or fetus during pregnancy can result in brain defects, some of which resemble those found in children with fetal alcohol syndrome. It has been hypothesized that ethanol may act to mediate alcohol-related birth defects in part by altering thyroid hormone system function. We investigated whether a binge pattern of maternal ethanol consumption over the last trimester equivalent of gestation in sheep results in an alteration in fetal or maternal thyroid function. Methods: Pregnant ewes received saline or ethanol beginning on day 109 of gestation (term, 145 days) for three consecutive days per week followed by 4 days without exposure. The fetuses were surgically instrumented on day 113, and experiments were performed on days 118 or 132. Fetal and maternal blood samples were collected, and plasma tri-iodothyronine (T3), thyroxine (T4), and free T4 concentrations were measured. Results: Fetal T3 and T4 on day 118, fetal T3 on day 132, and maternal T3 on day 132 were lower in response to ethanol. Fetal and maternal free T4 and maternal T4 did not change in response to ethanol. Fetal thymus and adrenal weights were reduced in response to ethanol. Conclusions: We conclude that, in sheep, maternal ethanol exposure during the third trimester equivalent resulting in blood ethanol concentrations that are commonly achieved by ethanol abusers decreases circulating thyroid hormone concentrations in the mother and fetus and fetal thyroid and thymus mass.